Pediatric Acrodermatitis Enteropathica

Updated: Nov 03, 2021
  • Author: KN Siva Subramanian, MD, FAAP; Chief Editor: Dirk M Elston, MD  more...
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Overview

Background

Acrodermatitis enteropathica (AE) is the clinical manifestation of zinc deficiency. Classically, it is a rare, autosomal recessive disorder, but more often it is a result of a nutritional or malabsorptive state. In either case, the signs and symptoms that occur during infancy and childhood always include a periorofacial and acral dermatitis that can have different primary morphologic appearances, which reflect the plasma zinc level and the length of time, whether chronic or acute, zinc depletion has been present (see image below). The classic triad of periorofacial and acral dermatitis, diarrhea, and alopecia is observed in fewer than one third of cases. Irritability, behavioral changes, and other neurologic disturbances, as well as recurrent infections and failure to thrive, may obfuscate the diagnosis. Adequate zinc replacement should rapidly improve signs and symptoms. However, a number of other inborn errors of metabolism or diseases characterized by malnutrition may mimic acrodermatitis enteropathica and these have been termed acrodermatitis dysmetabolica.

Skin lesions in the diaper area. Skin lesions in the diaper area.

See 13 Common-to-Rare Infant Skin Conditions, a Critical Images slideshow, to help identify rashes, birthmarks, and other skin conditions encountered in infants.

Also, see the 21 Hidden Clues to Diagnosing Nutritional Deficiencies slideshow to help identify clues to conditions associated with malnutrition.

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Pathophysiology

Zinc is an essential trace element. It is an integral part of numerous metallo-enzymes and transcription factors and is an important intracellular mediator, similar to calcium. Zinc stabilizes cell membranes by reducing free radicals and preventing lipid peroxidation. It is required for normal immune function, wound healing, and fertility. [1] Zinc deficiency also produces a loss of epidermal Langerhans cells. [2]

The gene SLC39A4 was found to encode a solute carrier protein called human zinc/iron-regulated transporterlike protein (hZIP4). [3] This protein controls zinc uptake across the plasma membrane of various cell types, including the intestine. [4] Protein hZIP4 transports zinc ions from the cell exterior or lumen of intracellular organelles into the cytoplasm, where it is available to other newly synthesized proteins. [5, 6, 7]

In infants with acrodermatitis enteropathica, an absence of this binding ligand may contribute to zinc malabsorption during weaning from breast milk. Such a ligand has been identified in normal pancreatic secretions, as well as in human milk.

A second genetic cause of acrodermatitis enteropathica is due to a genetic mutation in a breastfeeding mother. The SLC30A2 gene encodes a zinc transporter, ZnT2. A mutation in this gene causes decreased zinc secretion. In a nursing mother, this effectively decreases the zinc transfer from serum to breast milk, producing a transient zinc deficiency in an exclusively breastfed child. [8]

Other causes, such as high phytate concentrations found in cereals and soy milk, inhibit zinc absorption. Geophagia (consumption of soil or clay) also decreases zinc absorption. [9]

Acrodermatitis enteropathica has been reported as a presentation of food allergy. Serum total immunoglobulin E (IgE) and food-specific IgE levels to milk, soybean, wheat, and peanut have been measured to evaluate for food allergy. Undiagnosed food allergy can lead to profound zinc deficiency. Food allergy should be suspected in children with clinical symptoms of acquired acrodermatitis enteropathica. [10]

Transient, symptomatic zinc deficiency has been reported in breastfed, low-birthweight, premature infants and should be considered a rare but important disorder hallmarked by periorificial and acral dermatitis, with symptoms disappearing when nursing ends. [11] These reports illustrate the importance of zinc in rapidly growing preterm infants.

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Etiology

Zinc deficiency causes all the aforementioned clinical symptoms, which are easily and rapidly reversible with zinc supplementation, unless other concurrent diseases are present (eg, cystic fibrosis).

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Epidemiology

Frequency

The estimated prevalence for inherited cases is 1 case per 500,000 population.

Race

No race predilection is reported.

Sex

No sex predilection is reported.

Age

The age of presentation depends on the underlying etiology of the zinc deficiency. Inadequate intake of zinc may occur in a neonate or young infant who is exclusively breastfed from a mother with the SCL30A2 genetic mutation or a premature infant receiving inadequate zinc supplementation, given the increased need and decreased body stores. Excessive loss of zinc through digestive fluids or increased urinary excretion (as in the case of diuretic use or nephrotic syndrome) can present at any age, from infancy to adulthood. In addition, malnutrition can cause a zinc deficiency that can present at any age. [12, 13]

Children with congenital acrodermatitis enteropathica typically develop symptoms in the first few months of life, when an infant is weaned from breastfeeding or during nursing in full-term infants as a result of zinc deficiency in breast milk (with either normal or low maternal plasma zinc levels).

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Prognosis

Untreated patients with classic acrodermatitis enteropathica usually die in the first few years of life. They have severe growth restriction, diarrhea, dermatitis, alopecia, secondary bacterial and fungal infections, and neurologic and behavioral changes. All of these conditions are reversible with therapy.

Patients with acrodermatitis enteropathica uniformly respond to zinc therapy with a 100% survival rate. With zinc supplementation, various symptoms completely resolve or substantially improve.

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Patient Education

Provide information regarding zinc deficiency as the cause of acrodermatitis enteropathica. Emphasize the importance of lifelong compliance with taking zinc supplements.

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